Broad-Spectrum Antivirals: The Future of HIV Treatment?

By Warren TongFrom TheBody.com

May 16, 2012

Could a single drug be used to treat a variety of viruses -- potentially all viruses, including HIV? At least three novel approaches are being worked on to create such a drug, also known as a broad-spectrum antiviral.

Broad-spectrum drugs already exist in other areas of medicine. For instance, we have antibiotics to treat a wide range of bacterial infections. Unfortunately, while antibiotics work great at thwarting bacteria, they are largely ineffective against viruses.

Presently we have different antivirals that tend to treat specific diseases (e.g., Tamiflu only treats influenza, and most HIV medications only treat HIV). However, as people with HIV are well aware, viruses mutate and grow resistant to current antivirals.

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WIRED recently published an article highlighting three new approaches to antiviral treatment that may be able to stop a wide range of viruses, but without the risk of the viruses becoming resistant.

Prosetta: Chipping Away the Virus's Shell

Before he founded the biotech company Prosetta, researcher Vishwanath Lingappa, M.D., Ph.D., realized that viruses use proteins, taken from the very host cells they infected, as building blocks in producing the protective shells that exist around new, replicated viruses. Lingappa used this knowledge as a basis for his attempt to develop a broad-spectrum antiviral.

Instead of developing a drug to target the virus itself, which could then evolve and grow resistant, Prosetta's approach aims to alter the proteins in our own cells -- without damaging our cells in the process. "Prosetta's molecules bind to the proteins that viruses need to create their shells, stopping the maturation process. And because these proteins come together only to make viruses, the drugs should be nontoxic to patients," WIRED reports.

When asked how Prosetta's drug might fare against HIV, Lingappa told TheBody.com, "Our approach appears to work for all families of viruses, including the Retroviridae, of which HIV is a member. One of the nice things about this approach is that resistance is extremely unlikely to develop to these compounds, since they target the host, not the virus. Moreover, the compounds appear to do so in ways that are essential for the virus but not for the host."

Lingappa added that his team has been able to identify chemical compounds "that have proven highly active against HIV" in lab tests, and he is excited for Prosetta's potential in terms of a possible cure for HIV. But he also knows there is a long road ahead.

Interferon: The Next Generation

People living with hepatitis C are likely familiar with interferon, which has been a fundamental part of hep C treatment for years. Interferon is a protein made by our immune system to fight off viruses, bacteria, tumors and other unwelcome visitors. Interferon treatments, such as PegIntron and Pegasys, boost the body's ability to fight back.

However, many viruses prevent interferons from being made. And interferon treatments on the market often have their limitations and side effects.

Eleanor Fish, Ph.D. of the University of Toronto and other researchers are looking into developing a better version. "They've created synthetic interferons that last days instead of hours and will wipe out hepatitis C viruses completely in up to 81 percent of treated patients, depending on the strain," WIRED reports. "During Toronto's SARS outbreak, Fish tested synthetic interferons on a small pool of patients and found that their lungs healed significantly faster than those of control patients."

These preliminary results are promising and more research could lead to a very effective broad-spectrum antiviral. (TheBody.com attempted to reach Fish to discuss how her approach might apply specifically to HIV, but was unable to do so before this article was posted.)

DRACO: The Kamikaze-Cell Approach

The third and perhaps most interesting method reported in WIRED is an antiviral in development named DRACO (Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer). It is being engineered to do two things: identify cells that are infected with a virus and trigger those infected cells to commit suicide. "Because viruses have never been exposed to Draco before, their counterattacks are useless. The infected cells die before the viruses can mature," WIRED notes.

In a paper published in PLoS One last July, lead researcher Todd Rider, Ph.D., and his team at the Massachusetts Institute of Technology (MIT) explained the science behind DRACO: The drug "selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells," they write. Lab testing has "shown that [the DRACOs] are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza."

DRACO has not been tested against HIV yet, but Rider told TheBody.com, "We have recently established collaborations to test DRACO against HIV and several other viruses of interest. We certainly hope that DRACO will be effective against HIV, and that it can be a true cure for the virus."

However, while Rider is hopeful, he added that his drug is still a very long way from being proven effective in humans. "Even in the best case, MIT, our collaborators, and companies to which we license this technology will need to do several more years of animal trials before any human drug trials can begin, and then the human trials will probably take at least a few years before DRACO could be approved for everyone to use."

So, while all three of these approaches show a lot of promise, we shouldn't get our hopes up just yet. There are dangers to be wary of. For instance, we still don't fully understand the viral ecology in our bodies. Just like some bacteria naturally live inside our bodies and are helpful to our health, we may also be a home for "good" viruses that we don't know about, but that help us stay healthy and maintain our bodies' equilibrium. Still, further research on these approaches is definitely welcome. Hopefully more good results will follow.

Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.

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